A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease

被引：9

作者：

Hao, Jingcan ^{[1
]}

Wang, Wenyu ^{[1
]}

Wen, Yan ^{[1
]}

Xiao, Xiao ^{[1
]}

He, Awen ^{[1
]}

Guo, Xiong ^{[1
]}

Yang, Tielin ^{[2
,3
]}

Liu, Xiaogang ^{[2
,3
]}

Shen, Hui ^{[4
,5
]}

Chen, Xiangding ^{[6
]}

Tian, Qing ^{[4
,5
]}

Deng, Hong-Wen ^{[4
,5
]}

Zhang, Feng ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Publ Hlth, Natl Hlth & Family Planning Commiss,Key Lab Trace, Xian, Peoples R China

[2] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Key Lab Biomed Informat Engn, Minist Educ, Xian, Peoples R China

[3] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Inst Mol Genet, Xian, Peoples R China

[4] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat & Bioinformat, New Orleans, LA USA

[5] Tulane Univ, Ctr Bioinformat & Genom, New Orleans, LA USA

[6] Hunan Normal Univ, Coll Life Sci, Lab Mol & Stat Genet, Changsha, Hunan, Peoples R China

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

KNEE OSTEOARTHRITIS; CANDIDATE GENES; LINKAGE; EXPRESSION; GROWTH; LOCI;

D O I：

10.1038/srep31792

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Kashin-Beck disease (KBD) is a chronic osteoarthropathy, which manifests as joint deformities and growth retardation. Only a few genetic studies of growth retardation associated with the KBD have been carried out by now. In this study, we conducted a two-stage bivariate genome-wide association study (BGWAS) of the KBD using joint deformities and body height as study phenotypes, totally involving 2,417 study subjects. Articular cartilage specimens from 8 subjects were collected for immunohistochemistry. In the BGWAS, ADAM12 gene achieved the most significant association (rs1278300 p-value = 9.25 x 10(-9)) with the KBD. Replication study observed significant association signal at rs1278300 (p-value = 0.007) and rs1710287 (p-value = 0.002) of ADAM12 after Bonferroni correction. Immunohistochemistry revealed significantly decreased expression level of ADAM12 protein in the KBD articular cartilage (average positive chondrocyte rate = 47.59 7.79%) compared to healthy articular cartilage (average positive chondrocyte rate = 64.73 +/- 5.05%). Our results suggest that ADAM12 gene is a novel susceptibility gene underlying both joint destruction and growth retardation of the KBD.

引用

页数：6

共 28 条

[1] An assessment of ADAMs in bone cells:: absence of TACE activity prevents osteoclast recruitment and the formation of the marrow cavity in developing long bones [J].